Both 3-phenyllactate and 4-hydroxyphenyllactate are antibacterial agents isolated from lactobacilli (Non-patent References 1-4).
3-phenyllactate has a wide spectrum of antibacterial activity, not just against Aspergillus ochraceus, Penicillium roqueforti, Penicillium citrinium, and other molds (Non-patent Reference 5), but also against Listeria monocytogenes, Staphylococcus aureus, Escherichia coli 0157, and other such harmful gram-negative and positive bacteria (Non-patent References 1, 2, 5-7). This wide spectrum of antibacterial activity suggests the possibility of utilizing 3-phenyllactate as a food additive. It is moreover a useful compound that can be utilized in other applications such as pharmaceuticals, agricultural chemicals and intermediates thereof, aromatic biopolymer plastics, liquid crystals, and other such functional materials, biocompatible (medical) materials, and the like.
Because both 4-hydroxyphenyllactate and 3-phenyllactate are similarly derived from lactobacilli, this suggests not only the possibility of utilization as a food additive, but the potential to serve as an antibacterial additive for other applications, as well as potential in pharmaceuticals, agricultural chemicals, or intermediates thereof.
With regard to methods for the manufacture of these compounds, numerous attempts at manufacturing optically active 3-phenyllactate have been reported (Patent Reference 1), but from an environment impact and cost standpoint, a new method of synthesis that does not use such chemical substances would be preferable. Furthermore, no techniques have been devised to date for large-scale production of high purity 4-hydroxyphenyllactate. Currently, test reagents derived through organic chemical synthesis and principally racemic products, i.e., mixtures of D- and L-isomers, are marketed in small quantities, but a synthesis method affording higher efficiency of generation would be preferable.
One potential means for solving these problems would be a method for synthesis of optically active 3-phenyllactate or 4-hydroxyphenyllactate by microbial culture or with enzymes, to produce the desired compound in large quantities without the use of catalysts, organic solvents, and other such chemicals.
Various lactobacilli are known to be 3-phenyllactate-producing bacteria (Non-patent References 5, 9-11), including the Asmomycota Geotrichum candidum (Non-patent Reference 2) and the propionic acid-producing bacteria Propionibacterium freudenreichii (Non-patent Reference 8).
However, with regard to research on the enzyme molecular level conducted in relation to production of 3-phenyllactate, only purification of D,L-lactate dehydrogenase from Lactobacillus. sp SK007 has been reported, in 2008 (Non-patent Reference 12). Moreover, there are only two examples to date of cloning the genes of enzymes exhibiting enzyme activity on phenylpyruvate, which is predicted to be a precursor of 3-phenyllactate: recombinant D,L-lactate dehydrogenase derived from Lactobacillus plantarum SK002 (Non-patent Reference 13), and recombinant glyoxylate reductase/hydroxypyruvate reductase derived from Rhizobium etli CFN 42 (Non-patent Reference 16). It is unclear how these would contribute to production of 3-phenyllactate.
Moreover, while Patent References 2 and 3 report optically active 3-phenyllactate-producing bacteria, these are undesirable mixtures of R and S isomers.
In Patent Reference 4, it is reported that an enzyme produced by the filamentous bacteria Mycelia sterilia (FERM BP-2671), a PF1022 substance-producing bacteria, acts on phenylpyruvate so as to reduce it, converting it to (R)-2-hydroxy-3-phenylpropionic acid.
However, there is currently no efficient way to obtain high-purity optically active 3-phenyllactate.
As noted above, a manufacturing method whereby it would be possible to obtain high-purity optically active 3-phenyllactate and 4-hydroxyphenyllactate in large quantities has yet to be devised, and there is an urgent need to develop one.